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Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models

Authors
 Ha-Yeon Shin  ;  Eun-Ju Lee  ;  Wookyeom Yang  ;  Hyo Sun Kim  ;  Dawn Chung  ;  Hanbyoul Cho  ;  Jae-Hoon Kim 
Citation
 CANCERS, Vol.14(3) : 829, 2022-02 
Journal Title
CANCERS
Issue Date
2022-02
Keywords
gynecologic cancer ; patient-derived xenograft ; prognostic markers
Abstract
Patient-derived xenografts (PDXs) are important in vivo models for the development of precision medicine. However, challenges exist regarding genetic alterations and relapse after primary treatment. Thus, PDX models are required as a new approach for preclinical and clinical studies. We established PDX models of gynecologic cancers and analyzed their clinical information. We subcutaneously transplanted 207 tumor tissues from patients with gynecologic cancer into nude mice from 2014 to 2019. The successful engraftment rate of ovarian, cervical, and uterine cancer was 47%, 64%, and 56%, respectively. The subsequent passages (P2 and P3) showed higher success and faster growth rates than the first passage (P1). Using gynecologic cancer PDX models, the tumor grade is a common clinical factor affecting PDX establishment. We found that the PDX success rate correlated with the patient's prognosis, and also that ovarian cancer patients with a poor prognosis had a faster PDX growth rate (p < 0.0001). Next, the gene sets associated with inflammation and immune responses were shown in high-ranking successful PDX engraftment through gene set enrichment analysis and RNA sequencing. Up-regulated genes in successful engraftment were found to correlate with ovarian clear cell cancer patient outcomes via Gene Expression Omnibus dataset analysis.
Files in This Item:
T202204801.pdf Download
DOI
10.3390/cancers14030829
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Kim, Hyo Sun(김효선)
Yang, Wookyeom(양우겸)
Chung, Da Wn(정다은)
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191226
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